Pesticides based on vicinal diols

ABSTRACT

Pesticides based on vicinal diols, are available to control arthropod ectoparasites such as  Pediculus Humanus, Dermatophagoides pteronyssinus, Musca domestica , the Blattidae,  Blatella Germanica , and  Periplaneta Americana , by introducing to the locus of an infestation of the pest, a composition containing as active ingredient a vicinal diol.

[0001] This invention relates to the use of hydroxy-substitutedhydrocarbyl compounds, particularly vicinal diols such as 1,2-alkyldiolsto control arthropod pests.

BACKGROUND TO THE INVENTION

[0002] There is a need for a class of pesticidal agents that is able tokill a wide range of common arthropod pests of humans, their companionanimals and livestock, notably those belonging to the phyletic classesArachnida (ticks and mites) and Insecta (cockroaches, fleas, flies,silverfish, lice). Given the intimate nature of the association of theseparasites with their human or animal hosts, such agents must, for anypractical purpose, be relatively non-toxic to the host. There is afurther need for a class of pesticidal agents that is able to kill awide range of arthropod pests on foliage, in the agriculture and gardensectors.

[0003] It is also advantageous that the pesticide in either case isecologically-friendly (i.e. biodegradable).

[0004] A large number of chemical compounds have been developed andmarketed as pesticidal agents. However, few satisfy the triple criteria(1) generalised toxicity to arthropod pests; (2) comparatively lowtoxicity to human and animal hosts and (3) good biodegradability.

OBJECTS OF THE INVENTION

[0005] An object of the present invention is to provide alternativepesticidal agents that will obviate or mitigate at least some of thedrawbacks of currently commercially available products. In particular itis an object to provide a method of control of arthropod.

SUMMARY OF THE INVENTION

[0006] Now it is discovered that vicinal diols satisfy the desiredcriteria very well. In particular, the current research has revealedthat certain compounds of the class of vicinal diols which have thechemical formula, R(OH)₂, wherein the hydroxyl groups occupy vicinalpositions and R is a hydrocarbyl chain that is optionally derivatised orsubstituted, offer remarkably good efficacy as pesticides of the desiredqualities. The limiting number of carbons in the R group is a matter ofongoing research. However, good results are observed where the compoundhas at least one hydrocarbyl chain of length n+2 atoms, wherein thevalue of n is preferably at least 2 carbons, and the vicinal hydroxylsoccupy a terminal position, preferably having hydroxyls at 1,2-positionssuch that the diol forms a head group with a lipophilic tail. Differingactivities are observed with changes in n value. This leads topreferences amongst them and differences in activity for lower alkylgroups in comparison with higher alkyl groups (C₆ and above). Thus n mayhave a value of up to 20, but compounds wherein n has a value of from 2to 12 inclusive are of particular interest currently. Such diols arechiral in nature with, for example, the second carbon being a chiralcentre in the case of 1,2 diols. A racemic mixture is usefully employedin the present invention but single optical isomers (enantiomers), ormixtures containing a preponderance of one or more particular opticalisomer(s) can also serve the purposes of the invention. For example bothenantiomers of 1,2-decanediol have been shown to be effective againstlice in comparable fashion to the racemic mixture whose results aretabulated hereinafter.

[0007] The use of 1,2-alkyldiols for the control of bacterial infectionhas already been shown. Kazunori (Japanese patent application No. JP50-15 925/Publication No. 51-91 327) teaches that 1,2-alkyl diols,especially medium-chain homologues (n=5-9), are efficient bacteria- andfungi-static agents with general application. Similarly Pugliese (U.S.Pat. No. 4,049,830) teaches the application of 1,2-alkyl diols for thesterilisation of bovine teats as a prophylactic treatment for bacterialbovine mastitis. Similarly Greff (U.S. Pat. No. 6,123,953) teaches theuse of 1,2-diols for generalised topical application in the control ofbacteria that cause skin ailments including mastitis, acne and dandruff.Similarly Agostini and Cupferman (European patent application EP 0 935960 A1) teach cosmetic formulations containing an 1,2-alkyl diol as anantibacterial agent.

[0008] Airs in GB 687 850 has taught the use of certain vicinal diols asinsect repellents together with known non-solvent insecticides. Thepotential for the application of vicinal diols as the active ingredientin the control of pests by killing them or their ova has not heretoforebeen considered. Lover and Singer et al (U.S. Pat. No. 4,368,207) teachthe use of a range of monohydric alcohols against lice, their ova, andmites. Similarly Lover and Singer et al teach the use of non-vicinal,particularly 1,3 diols, in United Kingdom patent UK 1 604 856. Thatpatent suggests such compounds for the control of ectoparasites andtheir ova.

[0009] It has now been discovered that vicinal diols, in a preferredembodiment the readily available 1,2 diols, have surprisingly enhancedpesticidal properties in comparison with mono-ols or non-vicinal diols.1,2-Alkyldiols may be used to kill a wide range of common arthropodpests, notably arachnids, such as ticks and mites, and insects, such asflies, cockroaches, silverfish and lice, and ovicidal effects can bedemonstrated. Moreover these are found to be biodegradable, andeminently suitable as valuable pesticides for a wide variety of uses andapplications.

[0010] Whilst the potency and efficacy of the vicinal diols per se isproven, so that the selected diols themselves are directly useful, inmost cases the target pests can be effectively combated with dilutedamounts thereof, and for some purposes preferred delivery forms willoffer additional technical advantages.

[0011] Accordingly, further according to the invention there areprovided formulations that are suitable for contact application of suchvicinal diols or their derivatives, comprising at least one such vicinaldiol in a physiologically tolerable carrier, for the control of specificpest-induced ailments of humans and animals, including head- orbody-louse infection, carpet mite infestation, sheep-scab mite infectionand blow-fly strike.

[0012] Typically the formulations will comprise compositions of thepreferred vicinal diols alone or in combination, together with suitableauxiliaries as required, with a carrier adapted to deliver an effectiveamount of the vicinal diol(s) to the locus of a pest infestation. Thecarrier will usually be selected with a view to prolonging contact withthe target pest. Depending upon the infestation targeted, the carriermay be a finely divided solid or a liquid, and may be selected frompowder, resins, and aqueous or organic fluids. Therefore, a suitableformulating aid may be selected from liquid vehicles, solid carriers,auxiliaries, emulsifiers, dispersants, resins, gums, adherents, diluentsand extenders.

[0013] The pesticidal composition may be suitably prepared for deliveryin a formulation selected from a solution, a dispersion, an emulsion, adusting powder, a paste, an aerosol, a cream, a foam, a coated substratee.g. tacky paper, a pellet or block e.g. as in a bait for a trap. Theskilled worker will observe the need to select a physiologically benignor tolerable carrier when the pest is to be combated directly upon alive host, and may select such carriers from pharmaceutically acceptablecarriers, especially those intended for topical application, to formcreams, gels, pastes and ointments, aerated (foam/mousse) compositionsor dusting powders e.g. talc.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The invention will now be described in more detail by way ofexample with reference where appropriate to the accompanying drawings inwhich:

[0015]FIG. 1 is a graph of LC₅₀ values found for a range of 1,2 diolsagainst the human body louse (Pediculus humanus); and

[0016]FIG. 2 is a further graph illustrating a relationship between diolchain length and egg-laying activity of treated lice.

[0017] The following results will serve to illustrate the utility ofselected vicinal diols against a range of pests but should not beconsidered to prescribe limits to their effectiveness against these orother organisms. Demonstration of efficacy of the selected vicinal diolsherein is not intended to exclude analogues thereof except as may bespecifically stated herein and attention is directed to the claimshereinafter which define the scope of the invention.

EXAMPLE 1

[0018] Efficacy Contra Pediculus humanus

[0019] The pesticidal efficacy of compositions provided by thisinvention is demonstrated firstly with regard to the human body louse(Pediculus humanus), using vicinal diols in tests according to acceptedindustry protocols.

[0020] The special value and unique nature of vicinal diols isillustrated in Tables 1 and 2 wherein the LC₅₀ values, measured in testsagainst lice, for a range of diols and mono-ols are tabulated. Table 1shows the surprising potency of the vicinal diols in comparison to 1,3and other non-vicinal diols. For example 1,2-decanediol is significantlysuperior to 1,3-decanediol and the benefit of the vicinal compounds isapparent in the Table for all the examples of chain length shown.

[0021] Table 2 shows similar superiority of the vicinal diols overmono-ols and some triols. The best mono-ol tested has only 36% of thepotency found for 1,2-decanediol. The superior potency of the vicinaldiols provides the benefit that they can provide effective control of apest even when applied in a less than ideal manner to the targetorganisms. A yet further benefit of these compounds is that they havebeen shown to be readily metabolised by common soil bacteria, derivedfrom several different locations, and so will biodegrade readily whendispersed in the environment. TABLE 1 LC₅₀ value Potency index* CompoundDiol Type (mMol) (%) 1,2-Butanediol Vicinal >700 Not effective1,3-Butanediol Non-vicinal >2000 Not effective 1,2-HexanediolVicinal >200  6 1,5-Hexanediol Non-vicinal Not calculable Not effective1,6-Hexanediol Non-vicinal Not calculable Not effective 2,5-HexanediolNon-vicinal Not calculable Not effective 1,2-Octanediol Vicinal 40  301,3-Octanediol Non-vicinal >400 Not effective 1,2-Decanediol Vicinal 12100 1,3-Decanediol Non-vicinal 40  30

[0022] TABLE 2 LC₅₀ value *Potency Index Compound (mMol) (%)1,2,3-Hexanetriol Not calculable Not effective 1,2,6-Hexanetriol Notcalculable Not effective 2-Ethyl-1-hexanol 300  4 2-Ethyl-1,3-hexanediol 60  20 1-Decanol  35  32 2-Decanol  37  34 4-Decanol 183  69-Decene-1-ol  33  36 1,2-Decanediol  12 100 3-Ethyl-1-decanol  62  203-Octyl-1,2-decanediol  97  12 3-Ethyl-1,2-decanediol Not calculable Noteffective

[0023] The effect of diol chain length on activity is illustrated inFIG. 1, by way of a graph of the LC₅₀ values found for a range of 1,2diols against the human body louse.

[0024] These results show that 1,2 diols have pediculicidal activity, tothe extent that C₄ to C₁₆ diols are active, and those from C₈ to C₁₄ arepreferred, with the most preferred being 1,2-octanediol, 1,2-decanedioland 1,2-dodecanediol.

[0025]FIG. 2 demonstrates a further a beneficial property of the subjectmatter of the invention, namely the inhibition of egg laying, animportant feature in that the life cycle of the target organism isinterrupted when egg laying is inhibited or stopped. This is observed byconsidering the graphic illustration of efficacy of a range of diolswhich shows that as diol chain length increases egg laying activity oftreated lice declines substantially. 1,2-Octanediol is especiallyefficacious in the prevention of egg laying.

[0026] Ovicidal activity has been observed but research on this aspectof activity is continuing and the data is not included in thissubmission.

EXAMPLE 2

[0027] Efficacy Contra Dermatophagoides pteronyssinus

[0028] The utility of the vicinal diols is further illustrated by theresults of experiments against the house dust mite Dermatophagoidespteronyssinus according to accepted industry protocols. Mites weresealed in a cotton envelope and briefly immersed (5 seconds) in dilutesolutions (2.5%) of selected diols. The mites were examined one hourafter immersion and mortality calculated. The results are shown in Table3 below with comparative results for a proprietary carpet shampoo,permethrin insecticide and water (as controls). TABLE 3 MortalityTreatment (%) 1,2-Octanediol  65 1,2-Decanediol  95 Water  3 3% carpetshampoo  3 0.25% Permethrin 100

EXAMPLE 3

[0029] Efficacy Contra Musca domestica

[0030] A further example of the use of the compounds of the presentinvention is shown by testing decane-1,2-diol against house flies in astandard industry protocol for insecticides. More than 80% mortality wasobserved after 24 hours contrasting with decane-1,10-diol which did notexhibit insecticidal activity.

EXAMPLE 4

[0031] Formulation and Application

[0032] Vicinal diols are readily formulated in aqueous systems usingnon-toxic co-solvents such as isopropyl alcohol or by use of surfactantssuch as Tween®. This makes them eminently suitable for inclusion intomany household or industrial, pesticidal or cleansing products. Inparticular they can be incorporated into pharmaceutical preparations foruse on humans or animals. The treatment of lice and cockroaches withformulations containing 1,2-octanediol or 1,2-decanediol is tabulated inTable 4 along with control results for the solvent systems employed. Ina procedure following standard industry protocols the subject animalswere immersed for a few seconds in the test formulations and blotteddry. Mortality after 24 hrs was measured for the lice, after 1 hr forthe cockroaches. TABLE 4 Lice mortality Cockroach mortality Treatmentafter 24 hr (%) after 1 hr (%) 1,2-Octanediol in 100 100 1.5% Tween20 ®1,2-Octanediol in 50% 100 100 isopropyl alcohol 1,2-Decanediol in 7% 100100 Tween20 ® 1,2-Decanediol in 50% 100 100 isopropyl alcohol 0.25%Permethrin in 100 100 Water Water  4  0 50% isopropyl alcohol  4  0 1.5%Tween20 ®  0  0 7% Tween20 ®  13  0

INDUSTRIAL APPLICABILITY

[0033] In view of the aforesaid advantages and pesticidal properties ofthe compounds used in the compositions described herein, the inventionwill be usefully applied in dealing with pests encountered inagriculture, horticulture, human health, hygiene and veterinarymedicine.

1. A method of controlling pests which comprises applying to the locusof the pests or their ova, an effective amount of at least one vicinaldiol R(OH)₂, whereby the pests are killed or rendered moribund, whereinsaid vicinal diol is selected from the group consisting of diols whereinR represents a hydrocarbyl chain, that is optionally substituted orderivatised, with the proviso that the carbon in the chain next to thediol functionality shall not be ethyl-substituted, and the backbone ofthat chain comprises from 4 to 20 atoms.
 2. A method according to claim1, wherein the vicinal diol consists of an unsubstituted aliphatichydrocarbyl chain of n+2 atoms in the backbone thereof, wherein thevicinal diol hydroxyls occupy a terminal position, whereby the diolhydroxyls and the carbons to which they are attached form a head group,and n is an integer that has a value of at least
 2. 3. A methodaccording to claim 2, wherein n has a value not exceeding
 12. 4. Amethod according to claim 2, wherein n has an even value.
 5. A methodaccording to claim 2 or claim 3 or claim 4, wherein the vicinal diolhydroxyls occupy the 1,2-positions of the chain.
 6. A method accordingto claim 1, wherein the hydrocarbyl chain includes a hetero atom withinits length.
 7. A method according to claim 1, wherein the hydrocarbylchain is branched.
 8. A method according to claim 1, wherein thehydrocarbyl chain is partially unsaturated.
 9. A method according toclaim 1, wherein the hydrocarbyl chain is substituted with a functionalgroup, provided that said functional group is not a further hydroxylgroup adjacent to the vicinal diol functionality.
 10. A method accordingto claim 1, wherein the said vicinal diols are 1,2 diols.
 11. A methodaccording to claim 10, wherein the said vicinal diols are selected fromthe group consisting of linear aliphatic 1,2 diols of between 8 and 14carbon atom chain length.
 12. A method according to claim 10, whereinthe said vicinal diols are selected from the group consisting of linearaliphatic 1,2 diols of between 8 and 12 carbon atom chain length.
 13. Amethod according to claim 10, wherein the said vicinal diols areselected from the group consisting of 1,2-octanediol, 1,2-decanediol,and 1,2-dodecanediol.
 14. A pesticidal composition, particularly forcombating arthropod ectoparasites, containing as a pesticide, aneffective amount of at least one vicinal diol R(OH)₂, wherein saidvicinal diol is selected from the group consisting of diols wherein Rrepresents a hydrocarbyl chain, that is optionally substituted orderivatised, with the proviso that the carbon in the chain next to thediol functionality shall not be ethyl-substituted, and the backbone ofthat chain comprises from 4 to 20 atoms, in combination with aformulating aid selected from the group consisting of liquid vehicles,solid carriers, auxiliaries, emulsifiers, dispersants, resins,adherents, diluents and extenders.
 15. A pesticidal compositionaccording to claim 14, in a delivery formulation selected from the groupconsisting of a solution, dispersion, emulsion, dusting powder, gel,paste, aerosol, cream, foam, coated substrate, pellet, and block.
 16. Apesticidal composition according to claim 14 or claim 15, wherein thesaid vicinal diols are 1,2 diols.
 17. A pesticidal composition accordingto claim 16, wherein the said vicinal diols are selected from the groupconsisting of linear aliphatic 1,2 diols of between 8 and 14 carbon atomchain length.
 18. A pesticidal composition according to claim 16,wherein the said vicinal diols are selected from the group consisting oflinear aliphatic 1,2 diols of between 8 and 12 carbon atom chain length.19. A pesticidal composition according to claim 16, wherein the saidvicinal diols are selected from the group consisting of 1,2-octanediol,1,2-decanediol, and 1,2-dodecanediol.
 20. A pesticidal compositionaccording to claim 16 wherein the vicinal diol is 1,2-decanediol.
 21. Apesticidal composition according to claim 16 wherein the vicinal diol isa combination of 1,2-octanediol and 1,2-decanediol.
 22. A method forcontrolling lice comprising the application of a composition accordingto claim 14 or 15 to the locus of the lice infestation.
 23. A method forcontrolling lice according to claim 22, wherein the said compositioncontains an effective amount of 1,2-decanediol.
 24. A method forcontrolling lice according to claim 21, wherein the said compositioncontains an effective amount of a combination of 1,2-octanediol and1,2-decanediol.
 25. A method for controlling flies comprising theapplication of a composition according to claim 14 to the locus of aninfestation.
 26. A method for controlling flies comprising introducingto the locus of an infestation a bait or trap treated with a compositionaccording to claim
 14. 27. A method for controlling mites comprising theapplication of a composition according to claim 14, to the locus of aninfestation.
 28. A method for controlling cockroaches comprising theapplication of a composition according to claim 14, to the locus of aninfestation.
 29. A method for controlling cockroaches comprisingintroducing to the locus of an infestation a bait or trap treated with acomposition according to claim
 14. 30. A method of controlling a pestselected from the group consisting of Pediculus humanus,Dermatophagoides pteronyssinus, Musca domestics, the Blattidae, BlatellaGermanica, and Periplaneta Americana, comprising introducing to thelocus of an infestation of the pest, a composition containing as activeingredient a vicinal diol selected from the group consisting of1,2-octanediol, 1,2-decanediol, 1,2-dodecanediol, and combinationsthereof.
 31. A method according to claim 30, wherein the diol isintroduced as a formulation selected from the group consisting of asolution, dispersion, emulsion, dusting powder, gel, paste, aerosol,cream, foam, coated substrate, pellet and block.